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Biomedical subjects

C Ferri

Publications and source records attributed to C Ferri.

At least 73 records · Page 4Linked to original sources
PubMed1999

Ultrasonic videodensitometric analysis in scleroderma heart disease.

OBJECTIVES: Symptomatic cardiac involvement is a frequent visceral complication of systemic sclerosis that can affect the overall prognosis of the disease. The aim of the present study was to detect preclinical myocardial alterations in patients with systemic sclerosis using ultrasonic videodensitometric analysis. METHODS: Fifty patients with systemic sclerosis [five men, aged 48.8 +/- 11 years (mean +/- SD), range 22-65 years] with normal left ventricular function and 25 age- and sex-matched healthy controls were investigated. Exclusion criteria were the presence of positive maximal exercise stress, arterial hypertension, renal involvement and diabetes. Echocardiographic images were digitized using a real-time video-digitizer Quantitative texture analysis was performed on data from the septum and posterior wall, and mean gray level (MGL) histograms at both end-diastole (d) and end-systole (s) were obtained. The cyclic variation index (CVI) was calculated according to the formula [(MGLd - MGLs)/MGLd] x 100. Left ventricular mass, body surface corrected, was calculated according to the Penn convention. RESULTS: The pattern of variations of mean gray level during the cardiac cycle was totally different from that of the controls; this finding, probably related to myocardial fibrosis, was detected in the large majority of patients with systemic sclerosis (90%). In particular, CVI, which is the expression of the intrinsic myocardial structural function, was significantly lower than in controls (septum -31 +/- 38% versus 36 +/- 9%, P < 0.0001; and posterior wall -19 +/- 33% versus 51 +/- 20%, P < 0.0001). CONCLUSIONS: Ultrasonic videodensitometric analysis is a non-invasive, feasible method of detecting myocardial alterations in patients with systemic sclerosis, which could be related to both fibrosis and microcirculatory abnormalities. The potential role of these abnormalities in the pathogenesis of ventricular dysfunction should be investigated further.

Adult↗
PubMed1998

Immune response to an epitope of the NS4 protein of hepatitis C virus in HCV-related disorders.

NS4, a nonstructural protein of HCV, is a frequent target of antibodies in infected subjects. According to recent data, the antibodies frequently recognize the sequence 1921-40 of the NS4 protein. The aim of this work was to analyze antibody reactivity with the sequence 1921-40 in different HCV-related disorders. Although this sequence is located in a relatively invariant region of viral genome, two strain-specific sequences are described. Thus, three NS4 1921-1940 peptides were synthesized: the BK shared by most viral strains, the J6 (strain 2a), and the J8 (strain 2b). The peptides were used as antigens in the solid phase for measuring serum IgG antibodies in an ELISA assay. Antibodies reactive with the 1921-40 BK peptide were detected in 64% of sera from patients with autoimmune hepatitis (AIH), 51% from chronic hepatitis C (CHC), and 22% from mixed cryoglobulinemia (MC). The frequency of positive sera in MC was significatively lower than in AIH (P < 0.0001) or CHC (P < 0.0021). Similar results were obtained with the J6 and J8 peptides. All sera that did not react with the BK peptide were negative on J6 and J8 and conversely most sera reacting with the BK peptide also bound the J6 and the J8 peptides. No correlation was found between the genotype of the infecting virus and the presence of antibodies to any of the NS4 peptides. These results indicate that many HCV-infected subjects produce antibodies to the NS4 sequence 1921-40. The immune response to this sequence is not strain specific and varies with the different disorders associated with HCV infection.

Amino Acid Sequence↗
PubMed1998

Reduction of oxidative stress by oral N-acetyl-L-cysteine treatment decreases plasma soluble vascular cell adhesion molecule-1 concentrations in non-obese, non-dyslipidaemic, normotensive, patients with non-insulin-dependent diabetes.

To assess in vivo effects of antioxidants on vascular cell adhesion molecule (VCAM)-1 expression, circulating soluble VCAM-1 and intraerythrocytic reduced glutathione (GSH) and GSH disulphide (GSSG) concentrations were evaluated in non-insulin-dependent diabetic patients without complications (9 men, 6 women, 48 +/- 6 years old) before and after 1 month of either oral N-acetyl-L-cysteine (1.200 mg/day) or placebo treatments, given in randomized, cross-over, double-blind fashion. Ten healthy subjects (7 men, 3 women, 52 +/- 4 years old) served as control subjects. Baseline plasma VCAM-1 concentrations were higher (p = 0.007) in non-insulin-dependent diabetic patients (707.9 +/- 52.5 ng/ml) than in control subjects (627.3 +/- 84.6 ng/ml). Intraerythrocytic GSSG content was higher (non-insulin dependent diabetic patients: 0.618 +/- 0.185 micromol/g Hb; control subjects: 0.352 +/- 0.04 micromol/g Hb, p = 0.0002), whereas intraerythrocytic GSH concentrations were lower (p = 0.001) in non-insulin dependent diabetic patients (6.0 +/- 0.7 micromol/g Hb) than in control subjects (7.1 +/- 0.5 micromol/g Hb). The mean GSH:GSSG ratio was also lower (p = 0.0001) in the first (10.9 +/- 4.5) than in the second group (20.2 +/- 1.4). Circulating VCAM-1 and intraerythrocytic GSH concentrations were negatively correlated in non-insulin diabetic patients (r = 0.605, p = 0.01). Treatment with N-acetyl-L-cysteine decreased plasma VCAM-1 (p = 0.01) and intraerythrocytic GSSG (p = 0.006) but increased GSH concentrations (p = 0.04) and the GSH:GSSG ratio (p = 0.004) in non-insulin dependent diabetic patients. Our data indicate that the vascular endothelium is activated in non-insulin dependent diabetes. Antioxidant treatment counterbalanced such endothelial activation. Thus, antioxidant agents might protect against oxidant-related upregulation of endothelial adhesion molecules and slow down the progression of vascular damage in non-insulin dependent diabetes.

Acetylcysteine↗
PubMed1998

Influence of reduced glutathione infusion on glucose metabolism in patients with non-insulin-dependent diabetes mellitus.

To evaluate the relationship between oxidative stress and glucose metabolism, insulin sensitivity and intraerythrocytic reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio were measured in 10 non-insulin-dependent diabetes mellitus (NIDDM) patients and 10 healthy subjects before and after the intravenous administration of GSH. In particular, after baseline insulin sensitivity was assessed by a 2-hour euglycemic hyperinsulinemic clamp, either glutathione (1.35 g x m2 x min(-1)) or placebo (saline) were infused over a period of 1 hour. The same protocol was repeated at a 1-week interval, in cross-over, according to a randomized, single-blind design. In healthy subjects, baseline intraerythrocytic GSH/GSSG ratio (P < .0005) and total glucose uptake (P < .005) were significantly higher than in NIDDM patients. In the same subjects, GSH infusion significantly increased total glucose uptake (from 37.1 +/- 6.7 micromol kg(-1) x min(-1) to 39.5 +/- 7.7 micromol x kg(-1) x min(-1), P < .05), whereas saline infusion was completely ineffective. In addition, the mean intraerythrocytic GSH/GSSG ratio significantly increased after GSH infusion (from 21.0 +/- 0.9 to 24.7 +/- 1.3, P < .05). Similar findings were found in diabetic patients, in whom GSH infusion significantly increased both total glucose uptake (from 25.3 +/- 9.0 micromol x kg(-1) x min(-1) to 31.4 +/- 10.0 micromol x kg(-1) x min(-1), P < .001) and intraerythrocytic GSH/GSSG ratio (from 14.8 +/- 4.1 to 21.7 +/- 6.7, P < .01). Pooling diabetic patients and controls, significant correlations were found between intraerythrocytic GSH/GSSG ratio and total glucose uptake (r = .425, P < .05), as well as between increments of the same variables after GSH infusion (r = .518, P < .05). In conclusion, our data support the hypothesis that abnormal intracellular GSH redox status plays an important role in reducing insulin sensitivity in NIDDM patients. Accordingly, intravenous GSH infusion significantly increased both intraerythrocytic GSH/GSSG ratio and total glucose uptake in the same patients.

Adult↗
PubMed1998

Progressive sensorineural hearing impairment in systemic vasculitides.

OBJECTIVES: A large series of patients with various forms of systemic vasculitis were evaluated to analyze the prevalence of progressive sensorineural hearing loss (PSNHL), its characteristics and evolution, and the effects of different therapies. METHODS: A total of 673 patients were questioned about the presence of subjective audiovestibular disturbances. Of those, 80 subjects complained of subjective audiological disturbances and underwent oto-rhino-laryngological and audiovestibular evaluation. Those patients with progressive hearing impairment were selected and studied carefully. RESULTS: A PSNHL was observed in 14 patients. The hearing loss was bilateral and asymmetrical in most subjects. It was usually sensorineural, with a cochlear lesion. Unsteadiness was the most frequent vestibular symptom and canal paresis or palsy was noted in most patients. Systemic corticosteroids and cyclophosphamide were useful treatments; in unresponsive patients, satisfactory results were obtained with methotrexate and plasma exchange. CONCLUSIONS: PSNHL is a rare complication of systemic vasculitis, but occasionally is one of the presenting symptoms. Its clinical evolution is variable, but timely clinical assessment and treatment can positively affect prognosis.

Adrenal Cortex Hormones↗
PubMed1998

Enhanced activity of sodium-lithium countertransport in patients with cardiac syndrome X: a potential link between cardiac and metabolic syndrome X.

OBJECTIVES: This study was aimed at assessing both stimulated insulinemia and the sodium-lithium countertransport in a selected group of patients with cardiac syndrome X. BACKGROUND: Hyperinsulinemia, which is frequently present in patients with cardiac syndrome X, is often associated with an enhanced activity of the sodium-lithium countertransport, an in vitro marker of sodium-hydrogen exchange. METHODS: Fifteen patients with syndrome X and 14 matched controls were studied. After pharmacological washout, sodium-lithium countertransport was assessed from lithium-loaded red blood cells. Postload insulin levels were evaluated by a double-antibody radioimmunoassay. RESULTS: Maximal velocity of sodium-lithium countertransport was higher in patients with syndrome X compared to controls (635+/-200 vs. 324+/-49 micromol/liter/h, p = 0.001). Fourteen of the 15 patients with syndrome X (93%) presented sodium-lithium countertransport values higher than the mean +2 SD of the control group. At 120 min, 12 patients with syndrome X (80%) had plasma levels of insulin >420 pmol/liter, which corresponds to the mean value +2 SD of controls (p = 0.006). CONCLUSIONS: Both enhanced activity of the sodium-lithium countertransport and stimulated hyperinsulinemia are present in the vast majority of patients with cardiac syndrome X. As enhanced activity of the sodium-lithium countertransport has the potential to cause both glucose intolerance and smooth muscle hyperreactivity, it might represent a common cause of the metabolic and vascular alterations frequently found in syndrome X.

Biological Transport, Active↗
PubMed1998

Role of plasma and urinary endothelin-1 in early diabetic and hypertensive nephropathy.

To evaluate the role of circulating and renal endothelin-1 (ET-1) in early diabetic nephropathy, plasma ET-1 levels and urinary ET-1 excretion were evaluated in lean, normotensive patients affected by non-insulin-dependent diabetes (NIDDM) either with (n = 9, NIDDM+) or without microalbuminuria (n = 18, NIDDM-); in never-treated, lean, essential hypertensive patients with (n = 12, EH+) or without microalbuminuria (n = 10, EH-); and in healthy volunteers (n = 12). Results showed higher plasma ET-1 levels in NIDDM+ (1.97 +/- 0.58 pg/mL) than in NIDDM- (1.59 +/- 0.14 pg/mL, P = .013), EH+ (1.40 +/- 0.21 pg/mL, P = .005), EH- (0.91 +/- 0.19 pg/mL, P < .0001), and controls (0.60 +/- 0.10 pg/mL, P < .0001). The circulating ET-1 concentration was also higher in EH+ than EH- and controls (P < .0001). Urinary ET-1 excretion did not differ (P = .387, NS) between NIDDM+ (48.5 +/- 20.1 pg/min) and NIDDM- (40.9 +/- 21.6 pg/min), but was significantly reduced (P < .0001) in both groups compared with controls (70.0 +/- 15.5 pg/min). Similar findings were observed in hypertensive subgroups. No correlations were found between urinary ET-1 and other variables, including plasma ET-1 levels, in all groups. In conclusion, NIDDM+ is accompanied by a significant increase in plasma ET-1 levels. A significant elevation of circulating ET-1 concentration was evident also in NIDDM-, suggesting that early abnormalities of ET-1 production might precede the microalbuminuric phase of diabetes-related renal damage.

Adult↗
PubMed1998

Microvascular involvement in systemic sclerosis: laser Doppler evaluation of reactivity to acetylcholine and sodium nitroprusside by iontophoresis.

OBJECTIVES: To investigate the skin vasodilatory response to iontophoretically applied acetylcholine (Ach), an endothelium dependent vasodilator, and to sodium nitroprusside (SNP), an endothelium independent vasodilator, in patients with systemic sclerosis (SSc). METHODS: Eleven SSc patients were preliminarily studied (10 females, mean age 40.5; mean disease duration 6.5 years), and 16 age and sex matched control subjects. By means of laser Doppler flowmetry skin blood flow was evaluated at third finger, at baseline, and after postischaemic hyperaemia test and during iontophoretically transcutaneous application of 1% solution of Ach and SNP. RESULTS: No significant differences in basal skin blood flow were detected between SSc patients and controls. Cutaneous vasodilatory response to ischaemia, Ach, and SNP was significantly less pronounced in SSc patients compared with controls (p < 0.001). Moreover, among SSc patients a lower (p < 0.05) vasodilatory response to Ach compared with ischaemia and SNP was recorded. CONCLUSIONS: These data confirm a reduction of skin digital vasodilatory reserve in SSc patients and suggest a defect of both endothelial dependent arteriolar relaxation and wall compliance in the pathogenesis of this dysfunction.

Acetylcholine↗
PubMed1998

Heart involvement in systemic sclerosis: an ultrasonic tissue characterisation study.

BACKGROUND: Clinicoepidemiological findings indicate that symptomatic heart involvement in patients with systemic sclerosis (SSc) predicts a very poor prognosis. At necropsy studies, SSc heart involvement without significant coronary lesions is characterised by patchy myocyte necrosis and contraction band necrosis with collagen replacement leading to myocardial fibrosis. There is a discrepancy between the frequency of clinically evident myocardial disease (25%) and autoptical myocardial fibrosis (81%). OBJECTIVE: The aim of this study was to detect preclinical myocardial alterations in SSc patients by ultrasonic videodensitometric analysis. METHODS: Thirty five SSc patients (three male, aged 48.6 (11) SD years, range 22-65) with normal ventricular function and 25 age and sex matched healthy controls were studied. All patients had a negative maximal exercise stress; in all cases arterial hypertension, renal involvement, and diabetes were excluded. Echocardiographic images were digitised by a real time videodigitiser (Tomtec Imaging Systems). Quantitative texture analysis was performed on data from the septum and the posterior wall, obtaining mean gray level histogram (MGL) at both end-diastole (d) and end-systole (s). The cyclic variation index (CVI), was calculated according to the formula ((MGLd-MGLs)/MGLd) x 100. Left ventricular mass (LVM), body surface corrected, was calculated according to Penn convention. RESULTS: Comparable systolic and diastolic blood pressure, LVM, diastolic and systolic function were recorded in both SSc patients and controls. In contrast, in SSc patients the CVI, which is the expression of the intrinsic myocardial structural function, was significantly lower than in controls (septum: -18 (28)% v 35 (10)%, p < 0.0001; and posterior wall: -13 (32)% v 50 (20)%, p < 0.0001). Changes in cyclic echo amplitude, probably related to myocardial fibrosis, were detected in the large majority of SSc patients (88%). CONCLUSIONS: Ultrasonic videodensitometric analysis represents a non-invasive, feasible method that can detect early myocardial changes in SSc patients, which could be related to both fibrosis and microcirculatory abnormalities. Their potential evolution towards ventricular dysfunction and their link with cardiac sudden death, because of severe conduction system or rhythm disturbances, should be further investigated.

Adult↗
PubMed1998

Clustering of endothelial markers of vascular damage in human salt-sensitive hypertension: influence of dietary sodium load and depletion.

The contributing role of vascular endothelium in the development of hypertension-related vascular damage is well accepted. Salt-sensitive hypertension is characterized by a cluster of renal, hormonal, and metabolic derangements that might favor the development of cardiovascular and renal damage. To evaluate endothelial involvement in salt-sensitive essential hypertension, plasma levels of several markers of endothelial damage such as endothelin-1 (ET-1), von Willebrand factor (vWf), and soluble (S-) adhesion molecules E-selectin, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and 24-hour urinary albumin excretion (UAE) were measured in 39 nondiabetic, nonobese, never-treated essential hypertensive patients after intermediate (120 mmol/d), high (220 mmol/d), and low (20 mmol/d) NaCl diets. Patients were classified as salt sensitive (n=18) or salt resistant (n=21) according to their blood pressure responses to changes in dietary NaCl intake. Salt-sensitive hypertensives showed higher plasma ET-1 (P<0.05), vWf (P<0.005), and S-E-selectin levels (P<0.04) and increased UAE (P<0.05) than salt-resistant hypertensives. By contrast, circulating S-ICAM-1 and S-VCAM-1 concentrations were not significantly higher in salt-sensitive (596. 56+/-177.05 ng/mL and 541.06+/-157.84 ng/mL, respectively) than salt-resistant patients (516.86+/-147.99 ng/mL and 449.48+/-158.91 ng/mL, respectively). During the intermediate NaCl diet, plasma ET-1 responses to oral glucose load were greater in salt-sensitive (P<0. 05) than in salt-resistant patients. A marked (P<0.05) hyperinsulinemic response to oral glucose load was evident in salt-sensitive but not salt-resistant patients after each diet. This study shows increased plasma levels of the endothelium-derived substances E-selectin, vWf, and ET-1 in salt-sensitive hypertensives. Our findings support the hypothesis that salt sensitivity is correlated with an increased risk for developing hypertension-related cardiovascular damage.

Adult↗
PubMed1998

Mixed cryoglobulinaemia: a cross-road between autoimmune and lymphoproliferative disorders.

Mixed cryoglobulinaemia (MC) is a systemic vasculitis, secondary to the deposition in small and medium-sized blood vessels of circulating immune complexes, mainly the cryoglobulins, and complement. MC is characterised by a typical clinical triad (purpura, weakness, arthralgias) and by one or more organ involvement: chronic hepatitis, glomerulonephritis, peripheral neuropathy, skin ulcers and diffuse vasculitis. In a limited number of MC patients, a malignancy, that is B-cell non-Hodgkin's lymphoma or hepatocellular carcinoma, may also develop. Hepatitis C virus (HCV) infection has been found in the majority of patients with MC; the frequency of HCV markers (91%) was significantly higher than other rheumatic diseases (6.4%), namely systemic lupus, Sjögren's syndrome, rheumatoid arthritis and systemic sclerosis, or healthy controls (1.2%). The HCV infection of lymphoid tissues may represent the remote event leading to B-lymphocyte proliferation responsible for autoantibodies and immune-complex production. In a similar way, HCV infection may also be involved in the pathogenesis of other autoimmune (glomerulonephritis, thyroiditis, lung fibrosis, autoimmune hepatitis, porphyria cutanea tarda) and lymphoproliferative disorders (monoclonal gammopathies, B-cell lymphomas). MC shares numerous clinico-serological and pathological features with the above disorders. HCV seems to be their common etiological agent; however, a variable combination of unknown co-factors (infectious, genetic, environmental) should be determinant for the appearance of different clinical patterns.

Autoimmune Diseases↗
PubMed1998

Early activation of vascular endothelium in nonobese, nondiabetic essential hypertensive patients with multiple metabolic abnormalities.

Circulating soluble E-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular adhesion molecule-1 (VCAM-1) concentrations were evaluated in 93 nonobese essential hypertensive patients, of whom 16 had impaired glucose tolerance and hyperlipidemia (group I); 25 had impaired glucose tolerance (group II); 28 had hyperlipidemia (group III); and 24 had no metabolic abnormalities (group IV). A group of 22 healthy volunteers served as a control group. All groups were without clinical or ultrasound evidence of vascular lesion and were matched for age, sex, and BMI. Endothelial soluble adhesion molecules were measured at baseline, during an oral glucose tolerance test, and after 12 weeks of either enalapril or placebo treatments. Plasma soluble E-selectin, ICAM-1, and VCAM-1 were higher (P < 0.05) in group I and II than in the other groups (group I: E-selectin, 96.1+/-27.1; ICAM-1, 304.0+/-102.1; VCAM-1, 626.1+/-156.2 microg/l. Group II: E-selectin, 88.0+/-18.0; ICAM-1, 268.0+/-84.1; VCAM-1, 594.1+/-140.9 microg/I. Group III: E-selectin, 70.1+/-18.1; ICAM-1, 195.1+/-68.0; VCAM-1, 495.9+/-110.1 microg/l. Group IV: E-selectin, 65.1+/-16.1; ICAM-1, 168.1+/-64.0; VCAM-1, 472.1+/-108.2 microg/l). Soluble adhesins levels were not higher than normal in groups III and IV. Plasma soluble ICAM-1 concentrations increased in group I after glucose administration and were directly correlated with 2-h insulin levels (r=0.648, P=0.007). Compared with placebo, 12 weeks of enalapril treatment significantly (P < 0.0001) reduced soluble E-selectin, ICAM-1, and VCAM-1. Decrements of soluble adhesins were not dependent on enalapril-related blood pressure changes. Therefore, an early endothelial activation was present in essential hypertensive patients with impaired glucose tolerance, regardless of the presence of hyperlipidemia. ACE inhibition counteracted such endothelial activation.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1998

Batimastat, a synthetic inhibitor of matrix metalloproteinases, potentiates the antitumor activity of cisplatin in ovarian carcinoma xenografts.

Batimastat (also known as BB-94) is a synthetic matrix metalloproteinase inhibitor that has shown antineoplastic and antiangiogenic activity in various tumor models. In this study, two human ovarian carcinoma (HOC) xenografts (HOC22 and HOC8) were used to investigate the effect of batimastat on the antineoplastic activity of cisplatin. Both xenografts produced ascites and solid lesions in the peritoneal cavity of nude mice. HOC cells were inoculated i.p. in nude mice, and treatment was started at different stages of the disease. Batimastat was administered alone or concurrently with or subsequent to cisplatin therapy. In all of the protocols, the response of HOC xenografts was confirmed by cytological analysis of ascites and histological examination of the organs in the peritoneal cavity. Treatment of nude mice bearing early-stage (3 days after tumor implantation) HOC22 or HOC8 with cisplatin or batimastat alone delayed tumor growth and increased the survival time of the mice, although all animals eventually died. In contrast, treatment with batimastat (60 mg/kg i.p. every other day, for a total of eight injections) concomitantly with cisplatin (4 mg/kg i.v., every 7 days for a total of three injections) completely prevented growth and spread of both xenografts, and all animals were alive and healthy on day 200. The potentiation of cisplatin's activity by batimastat was dose dependent and was observed in the treatment of both advanced (7 days after tumor inoculation) and late-stage (20 days after inoculation) tumor. The administration of batimastat following cisplatin therapy also led to significant improvement in the survival of mice compared to treatment with cisplatin alone. These results suggest a potentiation of the antineoplastic activity of cisplatin by batimastat and support the use of the two agents in combination in the treatment of ovarian cancer patients.

Animals↗
PubMed1998

Impact of fibroblast growth factor-2 on tumor microvascular architecture. A tridimensional morphometric study.

Three cell clones originated by transfection of human endometrial adenocarcinoma HEC-1-B cells with fibroblast growth factor-2 (FGF-2) cDNA and characterized by a different capacity to produce and secrete the growth factor were transplanted subcutaneously in nude mice. Corrosion casting of the tumor microvasculature of xenografts produced by injection of 2 x 10(6) or 10 x 10(6) FGF-2-B9 cells (which produce and secrete significant amounts of FGF-2), 10 x 10(6) FGF-2-A8 cells (which produce comparable amounts of FGF-2 but do not secrete it), or 10 x 10(6) control FGF-2-B8 cells (which produce only trace amounts of FGF-2) was performed after 14 days of growth. Interbranching distances, intervascular distances, branching angles, and vessel diameters were then determined using tridimensional stereo pairs of the casted tumor vascularity. When transplanted at the same concentration, FGF-2-B9 cells grew faster in nude mice compared with FGF-2-A8 and FGF-2-B8 clones. The total amount of new vessel formation was far higher in FGF-2-B9 tumors than in FGF-2-B8 or FGF-2-A8 tumors. Also, vessel courses were more irregular and blind-ending vessels and evasates were more frequent in FGF-2-B9 tumors. Moreover, FGF-2-B9 tumor microvasculature was characterized by a wider average vascular diameter and by an extreme variability of the diameter of each individual vessel along its course between two ramifications. No statistical differences were observed when the distribution curves of the values of intervascular distances, interbranching distances, and branching angles of the microvessel network were compared among the different experimental groups. The distinctive features of the microvasculature of FGF-2-B9 tumors were retained, at least in part, in the smaller lesions produced by injection of a limited number of cells. The data indicate that FGF-2 production and release confer to FGF-2-B9 cells the ability to stimulate the formation of new blood vessels with distinctive architectural features. Neovascularization of FGF-2-B9 lesions parallels the faster rate of growth of the neoplastic parenchyma. This does not affect the overall architecture of the microvessel network that appears to be primed by characteristics of the HEC-1-B tumor cell line and/or by the microenvironment of the host. To our knowledge, this work represents the first attempt to define the influence of a single, defined growth factor on the tridimensional tumor vascular pattern.

Adenocarcinoma↗
PubMed1997

Adenosine A2A receptors and neuroprotection.

The adenosine A2A receptor subtype is one of the four adenosine receptors that have been identified in the mammalian organism. In addition to being found in blood vessels, platelets and polymorphonuclear leukocytes, the A2A receptors are abundant in the central nervous system, especially in the striatum. The recent development of selective A2A receptor ligands, in particular of receptor antagonists, makes it possible to elucidate the function of A2A receptors in normal and altered conditions. Pharmacological studies have shown that A2A receptor antagonists are potentially effective for treatment of neurodegenerative processes such as Parkinson's disease. Their activity is attributed to the close anatomical and functional links between A2A receptors and dopaminergic pathways in the basal ganglia. More recently, A2A receptor antagonists have proved to be active in models of cerebral ischemia. While the mechanisms underlying the role of A2A receptors in the hypoxia/ ischemia processes remains to be clarified, it is recognized that A2A receptor antagonists counteract the effects of excitatory aminoacids, which are massively released after cerebral ischemia. Another function of A2A receptors is related to protection from seizures, but further studies are needed to elucidate their specific interaction, if any, with neuronal excitability. Altogether, the great advance recently made with the discovery of selective A2A receptor ligands provides increasing information on the function of A2A receptors and opens new perspectives for treatment of neurological disorders.

Adenosine↗